The impact of the NLRP3 pathway in the pathogenesis of non-alcoholic fatty liver disease and alcohol-related liver disease

The presence of hepatic steatosis and inflammation is increasingly associated with both metabolic and alcohol-related liver conditions. Both are on the increase globally and, apart from liver transplantation, there are no licensed therapies that target the full complement of disease features. The presence of some shared pathogenic mechanisms and histological features in NAFLD and ALD suggests that it may be possible to develop markers for prognostication or staging, or indeed new therapeutic tools to treat both conditions. One such example of an approach exists in the form of the NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway. Activation of the NLRP3 inflammasome results in hepatocyte pyroptosis, persistence, and amplification of liver inflammation and activation of profibrogenic signaling cascades. Thus, targeting elements of the pathway in NAFLD and ALD may provide a tractable route to pharmacological therapy. In this review, we summarize the contribution of this inflammasome to disease and review the current options for therapy.